Project Summary-Cancer Development and Progression (CDP) Program The Cancer Development and Progression (CDP) Program is one of three highly interactive research programs of the Mays Cancer Center (MCC) at the University of Texas Health San Antonio (UT Health SA). Patrick Sung, D.Phil. and Ratna K. Vadlamudi, Ph.D. are Co-Leaders of the Program. The CDP Program focuses on laboratory-based studies of fundamental problems in cancer etiology and progression and also clinical translation of our research findings. The Program has two thematic areas: 1) Genomic Repair and Epigenetics and 2) Tumor Microenvironment. Through these foci, the CDP Program continues to make important contributions toward the MCC?s goal of cancer prevention and treatment, particularly for those disproportionate in our largely Hispanic population in South Texas. The Program?s Specific Aims are to: 1) Pursue basic and translational research to discover cancer-specific genome alterations, DNA repair mechanisms, and epigenetic programming that can be effectively translated to the clinic; and 2) Discover mechanisms and identify new therapeutic targets for modulating tumor metastases, paracrine signaling, immune signaling, and metabolism. The CDP Program has 29 members. They represent eight different academic departments in the Long School of Medicine at UT Health SA, and one member is from the University of Texas at Austin. CDP Program members hold $11.7M in peer- reviewed cancer-related funding (47 grants; direct costs). NCI provides $1.7M in funding (through 12 grants). Over the last reporting period, CDP Program members have published 260 peer-reviewed papers. Of these, 26% were products of intra-programmatic collaborations, 21% of inter-programmatic collaborations, and 77% involved multi-institutional collaborations, including 84 (42%) publications with other NCI-designated Cancer Centers. CDP members continue to use Cancer Center-supported cores extensively in their research, most notably, Next Generation Sequencing, Biostatistics and Bioinformatics, Mass Spectrometry, Flow Cytometry, and Drug Discovery and Structural Biology facilities. CDP scientific accomplishments over the past five years have resulted in several paradigm-shifting findings, high-impact publications (e.g. Nature, Cell, Molecular Cell, Nature Communications), development of novel models for defining cancer development and progression mechanisms, an antibody-based therapeutic for metastatic breast cancer, new estrogen receptor-beta agonists for enhancing tumor suppression, and small molecule inhibitors for treating endocrine therapy resistance. CDP members ?including successful new recruits whose work expands our program?s focus ? work closely with the Experimental and Developmental Therapeutics (EDT) Program to move research into the clinic. Multiple grants are already underway to pursue these hypotheses, with others in review and planned for upcoming submissions. In the last reporting period, two clinical trials have begun to translate CDP findings: one testing S-equol in breast cancer (NCT02352025), and one testing imipramine in triple-negative breast cancer (NCT03122444).